As is well known, there is a need to develop methods that increase or optimize the productivity of meat-producing animals, including nonruminant and ruminant animals, to enhance food production. Known methods typically employ the use of growth permittants, that is the use of compounds such as antibiotics that help keep the animals free of disease to allow or permit the treated animals to grow at an enhanced level as compared to untreated animals. However, there is increased interest in metabolic modifiers that may or may not function as growth permittants, but still improve the feed conversion of animals through a different mechanism.
2-Deoxy-D-hexose derivatives are compounds that heretofore have not been known to improve the feed conversion of animals.
2-Deoxy-D-glucose is the most well known of the 2-deoxy-D-hexoses. 2-Deoxy-D-glucose is a structural analog of glucose that is known to act as a competitive inhibitor of the phosphohexoisomerase step of glycolysis causing a depression in intracellular glucose utilization [see: M. Rezek and E. A. Kroeger, "Glucose Antimetabolites and Hungar",
J. Nutr., 106, p. 143 (1976)]. The metabolic changes initiated by intravenous administration of 2-deoxy-D-glucose alter the intracellular energy balance and therefore constitute a stimulus for the release of epinephrine from the adrenal medulla [see: G. P. Smith and A. W. Root, "Effect of Feeding on Hormonal Responses to 2-Deoxy-D-Glucose in Conscious Monkeys", Endocrinology, 85, pp. 963-968 (1969)]. The result of such an effect is an increase in circulating glucose (hyperglycemia) and the mobilization of free fatty acids. The hyperglycemia following intravenous administration of 2-deoxy-D-glucose is further potentiated by a reduction in cellular intake of glucose; however, the accumulated glucose is eventually cleared from the circulation and deposited in the liver as glycogen.
Intracerebroventricular administration of 2-deoxy-D-glucose has been shown in the prior art to increase circulating plasma somatostatin, glucose, and glucagon concentrations [see: E. Ipp, V. Piran, H. Richter, C. Garberoglio, A. Moossa and A. H. Rubenstein, "Central Nervous System Control Peripheral Circulating Somatostatin in Dogs: Effect of 2-Deoxyglucose", 63rd Annual Meeting of the Endocrine Society, p. 104 (1981)] and to increase the concentration of free fatty acids without affecting plasma insulin levels [see: C. C. Coimbra, J L. Gross, and R. H. Migliorini, "Intraventricular 2-Deoxyglucose, Glucose, Insulin and Free Fatty Acid Mobilization", Am. J. Physiol., 236, pp. 317-327 (1979)]. Intravenous administration of 2-deoxy-D-glucose has been shown to slightly lower plasma somatostatin concentrations. 2-Deoxy-D-glucose also has been shown in the prior art to cause a prompt release of growth hormone [see: G. M. Grodsky, "The Chemistry and Functions of Hormones", In: Review of Physiological Chemistry, Lange Medical Publications, Los Altos, Calif., p. 493 (1975)], and to have antiviral activity [see: J. G. Spivack, W. H. Prusoff and T. R. Thomas, "A Study of the Viral Mechanism of Action of 2-Deoxy-D-Glucose," Virology, 123, pp. 123-138 (1982)]. In addition, 2-deoxy-D-glucose may stimulate the functional maturation of pancreatic B cells, insulin biosynthesis and proinsulin mRNA activity [see: S. Kagawa, K. Murakoso, K. Nakao, K-Mimura, and A. Matsuoka, "Maintenance of Pancreatic Endocrine Cells of the Neonatal Rat: Part VIII. Effect of 2-Deoxyglucose on Insulin Biosynthesis and Proinsulin mRNA Activity", Indian J. Biochem. Biophys., 23, pp. 127-132 (1986)].
Due to the metabolic effects of 2-deoxy-D-glucose, injection of rats, rabbits and ruminants with relative high doses of 2-deoxy-D-glucose results in increased hunger and a substantial stimulation of food intake [see: M. Rezek and E. A. Kroeger; and T. R. Houpt, "Stimulation of Food Intake in Ruminants by 2-Deoxy-D-glucose and Insulin" Am. J. Physiol., 227, pp. 161-167 (1974)].
All of the aforementioned effects of 2-deoxy-D-glucose known in the prior art have been observed using high dosages of 2-deoxy-D-glucose.